Fluticasone propionate is a corticosteroid indicated for the treatment of asthma and allergic rhinitis. It is also used to treat eosinophilic esophagitis. It is named as S-(fluoromethyl)-6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate-17-propanoate and has the following structure:

Salmeterol is a long-acting β2-adrenergic receptor agonist that is indicated for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It is named as (RS)-2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy) hexylamino]ethyl}phenol and has the following structure:

Salmeterol is typically administered as the xinafoate salt, the structure of which is well-known in the art.
The combination of salmeterol (as the xinafoate salt) and fluticasone propionate is marketed in the EU by Allen & Hanburys as Seretide®, using either the Evohaler® pressurised metered-dose inhaler (pMDI) or the Accuhaler® dry powder inhaler (DPI). The Accuhaler® uses blisters filled with a blend of the micronised active agents and lactose monohydrate. It is marketed in three dosage strengths, each providing 50 micrograms of salmeterol xinafoate and 100, 250 or 500 micrograms of fluticasone propionate. In the US, the product is called Advair® and the inhaler is called Diskus®.
Seretide® is indicated in the regular treatment of asthma where use of a combination product (long-acting β2-agonist and inhaled corticosteroid) is appropriate. This is where either: patients are not adequately controlled with inhaled corticosteroids and as needed inhaled short acting β2-agonist; or patients are already adequately controlled on both inhaled corticosteroid and long-acting β2-agonist.
Seretide® is also indicated for the symptomatic treatment of patients with COPD, with a FEV1<60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy. FEV1 is a measurement used in spirometry which means the forced expiratory volume in one second. This is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. The measurement of FEV1 is used by healthcare professionals to determine lung function.
Combination products are well established in the art and are known to improve patient convenience and compliance. A drawback of combination products is that control over the dose of the individual active ingredients is reduced. The primary concern over side effects is in respect of the β2-agonist, since the therapeutic window is narrower and β2-agonists are associated with serious adverse effects, including cardiac side-effects. However, it is also desirable to reduce the systemic exposure of the inhaled corticosteroids.
Thus, there is a requirement in the art for an improved fluticasone/salmeterol combination product which retains the therapeutic effect of both products, but which reduces the systemic exposure of the fluticasone.